Selectivity of chromatin-remodelling cofactors for ligand-activated transcription

Selectivity of chromatin-remodelling cofactors for ligand-activated transcription
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DOI:
10.1038/414924a
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发表时间:
2001-12-20
期刊:
影响因子:
64.8
通讯作者:
Tjian, R
Tjian, R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lemon, B;Inouye, C;Tjian, R

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已经鉴定了一系列调控蛋白和多亚基辅因子(1),其指导真核基因转录。然而,由于间接测定动物和细胞中转录的固有局限性,建立各种相关辅因子的特定功能一直很困难。在这里,我们描述了,使用一个集成的染色质依赖性重建转录反应,纯化和鉴定的多亚基辅因子(PBAF)(2),这是必要的配体依赖性转录核激素受体。一种高度相关的辅因子,人SWI/SNF 3和含ISWI的染色质重塑复合物ACF(4)都不能增强转录。我们还表明,核激素受体介导的转录激活需要TATA结合蛋白(TBP)相关因子(TAF)以及多亚基辅因子ARC(5)/CRSP 6。这些研究证明了参与基因调控的高度相关复合物之间的功能选择性,并有助于定义激活转录所需的一组更完整的因子和辅因子。
An array of regulatory protein and multi-subunit cofactors has been identified(1) that directs eukaryotic gene transcription. However, establishing the specific functions of various related cofactors has been difficult owing to the limitations inherent in assaying transcription in animals and cells indirectly. Here we describe, using an integrated chromatin-dependent reconstituted transcription reaction, the purification and identification of a multi-subunit cofactor (PBAF)(2) that is necessary for ligand-dependent transactivation by nuclear hormone receptors. A highly related cofactor, human SWI/SNF3, and the ISWI-containing chromatin-remodelling complex ACF(4) both fail to potentiate transcription. We also show that transcriptional activation mediated by nuclear hormone receptors requires TATA-binding protein (TBP)-associated factors (TAFs) as well as the multi-subunit cofactors ARC(5)/CRSP6. These studies demonstrate functional selectivity amongst highly related complexes involved in gene regulation and help define a more complete set of factors and cofactors required to activate transcription.